Clinical Significance of MiR-137 Expression in Patients with Gastric Cancer After Radical Gastrectomy

The dysregulation of miR-137 plays vital roles in the oncogenesis and progression of various types of cancer, but its role in prognosis of gastric cancer patients remains unknown. This study was designed to investigate the expression and prognostic significance of miR-137 in gastric cancer patients after radical gastrectomy. Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression of miR-137 in human gastric cancer cell lines and tissues in patients with gastric adenocarcinoma. Results were assessed for association with clinical factors and overall survival by using Kaplan-Meier analysis. Prognostic values of miR-137 expression and clinical outcomes were evaluated by Cox regression analysis. The results exhibited that the expression level of miR-137 was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-137 was associated with tumor cell differentiation, N stage, and TNM stage. Decreased miR-137 expression in gastric cancer tissues was positively correlated with poor overall survival of gastric cancer patients. Further multivariate Cox regression analysis suggested that miR-137 expression was an independent prognostic indicator for gastric cancer except for TNM stage. Applying the prognostic value of miR-137 expression to TNM stage III group showed a better risk stratification for overall survival. In conclusion, the results reinforced the critical role for the down-regulated miR-137 expression in gastric cancer and suggested that miR-137 expression could be a prognostic indicator for this disease. In addition, these patients with TNM stage III gastric cancer and low miR-137 expression might need more aggressive postoperative treatment and closer follow-up.     

Identification of Kininogen-1 as a Serum Biomarker for the Early Detection of Advanced Colorectal Adenoma and Colorectal Cancer

Background

Serum markers represent potential tools for the detection of colorectal cancer (CRC). The aim of this study was to obtain proteomic expression profiles and identify serum markers for the early detection of CRC.

Methods

Proteomic profiles of serum samples collected from 35 healthy volunteers, 35 patients with advanced colorectal adenoma (ACA), and 40 patients with CRC were compared using Clinprot technology. Using enzyme-linked immunosorbent assays (ELISAs), 366 sera samples were additionally analyzed, and immunohistochemistry studies of 400 tissues were used to verify the expression of kininogen-1 and its value in the early detection of CRC.

Results

Predicting models were established among the three groups, and kininogen-1 was identified as a potential marker for CRC using Clinprot technology. ELISAs also detected significantly higher serum kininogen-1 levels in ACA and CRC patients compared to controls (P<0.05). Furthermore, the area under the receiver operating characteristic curve (AUC) for serum kininogen-1 in the diagnosis of ACA was 0.635 (P = 0.003), and for serum carcinoembryonic antigen (CEA) was 0.453 (P = 0.358). The sensitivity, specificity, and accuracy of serum kininogen-1 for diagnosing Duke’s stage A and B CRC was 70.13%, 65.88%, and 67.90%, respectively, whereas serum CEA was 38.96%, 85.88%, and 63.58%, respectively. Moreover, immunohistochemistry showed that expression of kininogen-1 was significantly higher in CRC and ACA tissues than in normal mucosa (48.39% vs. 15.58% vs. 0%, P<0.05).

Conclusions

These results suggest that Clinprot technology provides a useful tool for the diagnosis of CRC, and kininogen-1 is a potential serum biomarker for the early detection of advanced colorectal adenoma and CRC.     

Clinical Significance of Frizzled Homolog 3 Protein in Colorectal Cancer Patients

Frizzled homolog 3 receptor was up-regulated in several gastrointestinal cancers such as esophageal and gastric cancers. Moreover, frizzled homolog 3 has recently reported to be expressed in colorectal adenoma specimens. In the present study, we investigated the clinical significance of frizzled homolog 3 protein in colorectal cancer patients. Using immunocytochemical staining, frizzled homolog 3 expression was examined in 186 colorectal cancer specimens, 79 colorectal adenoma specimens, 133 colorectal polyp specimens, 127 colorectal cancer specimens with lymph node and/or distant metastasis, 310 specimens of various non-colorectal cancer metastatic carcinomas and 40 specimens with simultaneous occurrence of colorectal cancer, colorectal adenoma and colorectal polyp. Statistical analysis was used to correlate frizzled homolog 3 protein expression to the clinicohistopathological factors, recurrence/metastasis and survival after follow-up for 42 months in colorectal cancer patients. Frizzled homolog 3 protein was expressed in 100% colorectal cancer specimens, 89% colorectal adenoma specimens, 75% colorectal polyp specimens and 69% normal colorectal epithelial tissues. Moreover, frizzled homolog 3 immunocytochemical scores were highly correlated with colorectal cancer progression. Furthermore, frizzled homolog 3 was expressed in a comparatively lower percentage of metastatic hepatocellular carcinoma and metastatic renal clear cell carcinoma with focal and very weak staining than other metastatic tumor types. On the other hand, the frizzled homolog 3 immunocytochemical scores of colorectal adenomas with synchronous colorectal carcinomas were significantly higher than those of pure colorectal adenomas. Statistical analysis showed that frizzled homolog 3 immunocytochemical scores were associated with Dukes stage and lymph node status. Finally, stratified groups of colorectal cancer patients had significant differences in their recurrence/metastasis and survival. In conclusion, the present large-scale study has clearly showed that frizzled homolog 3 protein can generate clinically important information for colorectal cancer patients.     

The Functional Significance of MicroRNA-29c in Patients with Colorectal Cancer: A Potential Circulating Biomarker for Predicting Early Relapse

Background

The recurrence of colorectal cancer (CRC) is frequent within the first year of curative resection surgery and may be unavoidable. microRNAs have been suggested to play roles in carcinogenesis and cancer recurrence. We recently identified microRNA-29c (miRNA-29c) as a predictor of early recurrence in CRC. In the present study, we further investigated the functions and serum level of miRNA-29c in relation to early recurrence of CRC.

Methods

First we further confirmed overexpression of miRNA-29c in non-early relapse subjects. Gain-of-function in vitro studies were used to evaluate the effect of miRNA-29c on cell proliferation, migration, invasion, and cell cycle progression. The colon cancer cell line Caco2 and a stable clone overexpressing miRNA-29c were xenografted to evaluate the in vivo effect of miRNA-29c in null mice. Finally, circulating miRNA-29c was investigated as a potential biomarker for identifying early relapse.

Results

miRNA-29c expression significantly decreased during early relapse compared to non-early relapse in UICC stage II and III CRC patients (P = 0.021). In vitro studies showed that overexpression of miRNA-29c inhibited cell proliferation and migration. The cell cycle studies also revealed that miRNA-29c caused an accumulation of the G1 and G2 population. In vivo, miRNA-29c suppressed tumor growth in null mice. The serum miRNA-29c increased significantly in early relapsed patients compared to non-early elapsed patients (P = 0.012).

Conclusions

miRNA-29c shows anti-tumorigenesis activity, and preoperative circulating miRNA-29c levels can be used to predict postoperative early relapse of CRC.     

Circulating MiR-133a as a Biomarker Predicts Cardiac Hypertrophy in Chronic Hemodialysis Patients

Background

MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form and have emerged as potential diagnostic markers in patients with cardiovascular disease. Our study aimed to assess circulating miR-133a levels in MHD patients and the relation of miR-133a to cardiac hypertrophy.

Methods

We profiled miRNAs using RNA isolated from the plasma of participants. The results were validated in 64 MHD patients and 18 healthy controls.

Results

Levels of plasma miR-133a decreased in MHD patients with LVH compared with those in healthy controls. Plasma miR-133a concentrations were negatively correlated with LVMI and IVS. After single hemodialytic treatment, plasma miR-133a levels remained unchanged. Cardiac Troponin I and T were not associated with LVMI and IVS.

Conclusions

Our observations supplied the possibility that circulating miR-133a could be a surrogate biomarker of cardiac hypertrophy in MHD patients.     

Prognostic Significance of CD26 in Patients with Colorectal Cancer

Background

CD26, dipeptidyl peptidase IV, was discovered firstly as a membrane-associated peptidase on the surface of leukocyte. We previously demonstrated that a subpopulation of CD26⁺ cells were associated with the development of distant metastasis, enhanced invasiveness and chemoresistance in colorectal cancer (CRC). In order to understand the clinical impact of CD26, the expression was investigated in CRC patient''s specimens. This study investigated the prognostic significance of tumour CD26 expression in patients with CRC. Examination of CD26⁺ cells has significant clinical impact for the prediction of distant metastasis development in colorectal cancer, and could be used as a selection criterion for further therapy.

Methods

Tumour CD26 expression levels were studied by immunohistochemistry using Formalin-fixed paraffin embedded (FFPE) tissues in 143 patients with CRC. Tumour CD26 expression levels were correlated with clinicopathological features of the CRC patients. The prognostic significance of tumour tissue CD26 expression levels was assessed by univariate and multivariate analyses.

Result

CD26 expression levels in CRC patients with distant metastasis were significantly higher than those in non-metastatic. High expression levels of CD26 were significantly associated with advanced tumour staging. Patients with a high CD26 expression level had significantly worse overall survival than those with a lower level (p<0.001).

Conclusions

The expression of CD26 was positively associated with clinicopathological correlation such as TNM staging, degree of differentiation and development of metastasis. A high CD26 expression level is a predictor of poor outcome after resection of CRC. CD26 may be a useful prognostic marker in patients with CRC.     

IGFBP3 Methylation Is a Novel Diagnostic and Predictive Biomarker in Colorectal Cancer

Background and Aim

Aberrant hypermethylation of cancer-related genes has emerged as a promising strategy for the development of diagnostic, prognostic and predictive biomarkers in human cancer, including colorectal cancer (CRC). The aim of this study was to perform a systematic and comprehensive analysis of a panel of CRC-specific genes as potential diagnostic, prognostic and predictive biomarkers in a large, population-based CRC cohort.

Patients and Methods

Methylation status of the SEPT9, TWIST1, IGFBP3, GAS7, ALX4 and miR137 genes was studied by quantitative bisulfite pyrosequencing in a population-based cohort of 425 CRC patients.

Results

Methylation levels of all genes analyzed were significantly higher in tumor tissues compared to normal mucosa (p<0.0001); however, cancer-associated hypermethylation was most frequently observed for miR137 (86.7%) and IGFBP3 (83%) in CRC patients. Methylation analysis using the combination of these two genes demonstrated greatest accuracy for the identification of colonic tumors (sensitivity 95.5%; specificity 90.5%). Low levels of IGFBP3 promoter methylation emerged as an independent risk factor for predicting poor disease free survival in stage II and III CRC patients (HR = 0.49, 95% CI: 0.28–0.85, p = 0.01). Our results also suggest that stage II & III CRC patients with high levels of IGFBP3 methylation do not benefit from adjuvant 5FU-based chemotherapy.

Conclusion

By analyzing a large, population-based CRC cohort, we demonstrate the potential clinical significance of miR137 and IGFBP3 hypermethylation as promising diagnostic biomarkers in CRC. Our data also revealed that IGFBP3 hypermethylation may serve as an independent prognostic and predictive biomarker in stage II and III CRC patients.     

Predictive Clinical Indicators of Biochemical Progression in Advanced Prostate Cancer Patients Receiving Leuplin Depot as Androgen Deprivation Therapy

Therapeutic planning and counseling for advanced prostate cancer patients receiving androgen deprivation therapy (ADT) is complicated because the prognoses are highly variable. The purpose of this study is to identify predictive clinical indicators of biochemical progression (BCP). In this retrospective analysis, data from 107 newly diagnosed patients (from November 1995 to April 2008) with advanced prostate adenocarcinoma receiving Leuprorelin acetate depot were analyzed. Data was collected from the computerized registry of two collaborating medical centers in Taiwan. Cox regression and Kaplan-Meier analyses were used to evaluate the relationship between potential predictive parameters and BCP. Univariate analysis revealed that predictors of BCP included (1) initial serum prostate-specific antigen (PSA) (hazard ratio [HR], 1.00; 95% confidence interval [CI] 1.00–1.00); (2) log of initial PSA (HR, 1.35; 95% CI 1.17–1.56); (3) PSA density at diagnosis (HR, 1.00; 95% CI 1.00–1.01), and (4) pathological bone fracture (HR, 2.22; 95% CI 1.20–4.11). Age (HR, 0.94; 95% CI 0.91–0.98) and hemoglobin levels (HR, 0.86; 95% CI 0.76–0.97) were also associated with greater risk of BCP. After adjusting for age, pathologic fracture, and hemoglobin level, the initial PSA and PSA density were no longer significantly associated with BCP. However, age and hemoglobin levels continued to be associated with greater risk of BCP (P≤0.007). Using Kaplan-Meier analysis, patients with higher initial PSA concentration, pathological bone fracture, and low hemoglobin had a greater probability of BCP. Thus, low hemoglobin and age are predictive indicators of BCP and therefore early indicators of BCP despite ADT therapy.     

DC-CIK细胞免疫治疗晚期结直肠癌患者的远期疗效及其影响因素分析

目的:探讨树突状细胞(DC)联合细胞因子诱导的杀伤(CIK)细胞免疫治疗晚期结直肠癌(CRC)患者的远期疗效及其影响因素分析。方法:收集我院2011年1月至2014年1月收治的112例晚期结直肠癌患者,依据是否接受DC-CIK细胞免疫治疗将患者分为对照组(n=47)和观察组(n=65),分别给予一般化疗方案治疗和化疗联合DC-CIK细胞免疫方案治疗,比较两组患者治疗前后血清肿瘤标志物癌胚抗原(CEA)、淋巴细胞亚群,治疗有效率(RR)、疾病控制率(DCR)、无进展生存期(PFS)和安全性改变,并分析影响疗效的危险因素。结果:两组治疗后CEA水平均显著低于治疗前(P0.05),治疗后对照组CD3+T细胞、CD4+T细胞、CD8+T细胞和NK细胞均显著减少(P0.05),观察组治疗后CD3+T细胞和CD8+T细胞数量显著高于治疗前和同期对照组(均P0.05);对照组RR、DCR和PFS分别为44.68%、65.96%、6.5个月,观察组治疗对应指标分别为46.15%、86.15%、9个月,观察组DCR和FPS均显著高于对照组(P0.05);多因素分析发现TNM分期达到Ⅳ级(P=0.023)和年龄超过60岁(P=0.006)是影响疗效的独立危险因素。结论:DC-CIK细胞免疫治疗晚期结直肠癌安全可靠,能显著改善患者免疫功能控制肿瘤进展,延长生存期,提高生存质量,值得临床推广。     

替吉奥联合伊立替康治疗晚期结肠癌的临床研究

目的:比较替吉奥联合伊立替康与替吉奥单药治疗晚期结肠癌的临床疗效。方法:选取2011年3月~2012年3月我院收治的晚期结肠癌患者90例,按照随机数字表法将患者分为研究组和对照组,每组45例,研究组给予替吉奥联合伊立替康,对照组给予替吉奥单药治疗,比较两组近期疗效、远期疗效和不良反应。结果:研究组的总有效率51.1%(23/45)显著高于对照组的26.7%(12/45),两组比较差异具有统计学意义(X2=13.281,P=0.017);研究组中位进展时间和中位生存时间均显著长于对照组,两组比较差异具有统计学意义(t=9.029,10.412,P=0.021,0.019);两组中性粒细胞减少和腹泻比较差异具有统计学意义(X2=11.517,12.041;P=0.023,0.019)。结论:替吉奥联合伊立替康治疗晚期结肠癌较单用替吉奥具有更好的治疗效果,值得临床推广应用。     

P53 Status as a Predictive Biomarker for Patients Receiving Neoadjuvant Radiation-Based Treatment: A Meta-Analysis in Rectal Cancer

Background

Numerous studies have yielded inconsistent results regarding the relationship between p53 status and the response to neoadjuvant radiation-based therapy in patients with rectal cancer. We conducted a meta-analysis to clarify the relationship between p53 status and response to radiation-based therapy in rectal cancer.

Methods/Findings

A total of 30 previously published eligible studies including 1,830 cases were identified and included in this meta-analysis. Wild-type form of p53 status (low expression of p53 protein and/or wild-type p53 gene) was associated with pathologic response in rectal cancer patients who received neoadjuvant radiation-based therapy (good response: risk ratio [RR] = 1.30; 95% confidence intervals [CI] = 1.14–1.49; p<0.001; complete response RR = 1.65; 95% CI = 1.19–2.30; p = 0.003; poor response RR = 0.85; 95% CI = 0.75–0.96; p = 0.007). In further stratified analyses, this association remained for sub-groups of good and poor response in neoadjuvant radiotherapy (RT) setting, good and complete response in chemoradiotherapy (CRT) setting. And the association between response and the presence of p53 gene mutations was stronger than that between response and protein positivity.

Conclusion

The results of the present meta-analysis indicate that P53 status is a predictive factor for response in rectal cancer patient undergoing neoadjuvant radiation-based therapy.     

Evaluating Predictive Pharmacogenetic Signatures of Adverse Events in Colorectal Cancer Patients Treated with Fluoropyrimidines

The potential clinical utility of genetic markers associated with response to fluoropyrimidine treatment in colorectal cancer patients remains controversial despite extensive study. Our aim was to test the clinical validity of both novel and previously identified markers of adverse events in a broad clinical setting. We have conducted an observational pharmacogenetic study of early adverse events in a cohort study of 254 colorectal cancer patients treated with 5-fluorouracil or capecitabine. Sixteen variants of nine key folate (pharmacodynamic) and drug metabolising (pharmacokinetic) enzymes have been analysed as individual markers and/or signatures of markers. We found a significant association between TYMP S471L (rs11479) and early dose modifications and/or severe adverse events (adjusted OR = 2.02 [1.03; 4.00], p = 0.042, adjusted OR = 2.70 [1.23; 5.92], p = 0.01 respectively). There was also a significant association between these phenotypes and a signature of DPYD mutations (Adjusted OR = 3.96 [1.17; 13.33], p = 0.03, adjusted OR = 6.76 [1.99; 22.96], p = 0.002 respectively). We did not identify any significant associations between the individual candidate pharmacodynamic markers and toxicity. If a predictive test for early adverse events analysed the TYMP and DPYD variants as a signature, the sensitivity would be 45.5 %, with a positive predictive value of just 33.9 % and thus poor clinical validity. Most studies to date have been under-powered to consider multiple pharmacokinetic and pharmacodynamic variants simultaneously but this and similar individualised data sets could be pooled in meta-analyses to resolve uncertainties about the potential clinical utility of these markers.     

Evaluation of lncRNA FOXD2-AS1 Expression as a Diagnostic Biomarker in Colorectal Cancer

Background:Colorectal cancer (CRC) is still considered one of the prevalent cancers worldwide. Investigation of potential biomarkers for early detection of CRC is essential for the effective management of patients using therapeutic strategies. Considering that, this study was aimed to examine the changes in lncRNA FOXD2-AS1 expression through colorectal tumorigenesis. Methods:Fifty CRC tumor tissues and fifty adjacent normal tissue samples were prepared and involved in the current study. Total RNA was extracted from the samples and then reverse transcribed to complementary DNA. Next, the expression levels of lncRNA FOXD2-AS1 were evaluated using real-time PCR in CRC samples compared to normal ones. Also, receiver operating characteristic curve analysis was used to evaluate the diagnostic value of FOXD2-AS1 for CRC.Results:The obtained results showed that the expression level of FOXD2-AS1 gene was significantly (p<0.0001) up-regulated in tumor tissues compared to normal marginal tissues. Also, a significant correlation was observed between higher the expression of FOXD2-AS1and the differentiation of tumor cells. Furthermore, ROC curve analysis estimated an AUC value of 0.59 for FOXD2-AS1, suggesting its potential as a diagnostic target.Conclusion:Taken together, the current study implied that tissue-specific upregulation of lncRNA FOXD2-AS1 might be appropriate diagnostic biomarkers for CRC. Nonetheless, more studies are needed to validate these results and further illustrate FOXD2-AS1 function through colorectal tumorigenesis.Key Words: Biomarker, Colorectal cancer, FOXD2-AS1, lncRNA, qRT-PC     

The Value of MiR-383, an Intronic MiRNA,as a Diagnostic and Prognostic Biomarker in Intestinal-Type Gastric Cancer

MicroRNAs, a class of gene expression regulatory non-coding RNAs, participate in the pathogenic mechanisms of gastric cancer which is one of the life-treating cancers. Due to its aberrant expression in some types of human cancer, miR-383 has the value of being investigated in relation to cancer treatment and diagnosis. MiR-383 is placed in intron of SGCZ, a protein-coding gene, which is subject to dysregulation in various diseases. The purpose of the current study was to investigate the contribution of miR-383 to intestinal-type gastric adenocarcinoma tumorigenesis. The expression level of miR-383 was investigated by qRT-PCR in pairs of tumorous and adjacent tumor-free tissues of 40 patients with gastric cancer during endoscopy. Also, the susceptibility of miR-383 as a tumor marker and the relationship between its aberrant expression and clinicopathological features were determined. qRT-PCR data showed that miR-383 was dysregulated during gastric tumorigenesis. MiR-383 was dramatically downregulated up to sevenfold in intestinal-type gastric adenocarcinoma compared with adjacent tumor-free tissues (P < 0.001). Misregulation of miR-383 did not reveal a significant correlation with clinical characteristics. The ROC area of 80% with 76% sensitivity and 84% specificity was determined by P < 0.001. The current study demonstrated downregulation of miR-383 in intestinal-type gastric adenocarcinoma. Downregulation of miR-383 might be used as a potential tumor marker for the diagnosis of gastric cancer or could be a potential target for gene therapy.     

结肠癌患者血清C反应蛋白检测的临床意义

目的:探讨结肠癌患者血清C反应蛋白检测的临床意义。方法:分别在术前1天及术后第15天测定77例结肠癌患者血清C反应蛋白的浓度,并与正常对照组进行比较。结果:结肠癌患者术前术后血清C反应蛋白显著高于正常对照组(P<0.01),术后尽管有显著下降,但仍高于正常对照组(P<0.05)。结论:血清C反应蛋白检测对评估结肠癌患者病情及预后有重要意义。     

CEA mRNA在大肠癌患者微转移早期预测中的意义

目的:大肠癌是最常见的恶性肿瘤之一,血行转移是大肠癌根治性手术失败的原因之一,在根治性切除肿瘤患者中,有大部分患者死于肿瘤的复发和转移,因此早期发现大肠癌微转移,对于延长患者预后指导下一步治疗具有重要意义。本研究已检测大肠癌患者外周血和引流静脉血中CEA mRNA的表达,以探索手术操作和微转移的关系,以及引流静脉血中微转移的发生与临床病理因素的关系,探讨早期发现大肠癌血循环微转移的意义。方法:应用逆转录多聚酶链式反应(RT-PCR)法检测大肠癌患者手术前,手术后外周血及引流静脉血液中的CEA mRNA水平。结果:(1)大肠癌患者术前外周血CEA mRNA阳性率26.7%(16/60),引流静脉血阳性率48.3%(29/60),引流静脉血明显高于外周静脉血(P0.05)。(2)大肠癌引流静脉血中CEA mRNA在肿瘤大于5厘米者、Dukes C期、中低分化程度、有淋巴转移者、浸及浆膜者比外周静脉血更有统计学上的意义。(3)手术前后引流静脉血CEAm RNA阳性率具有显著差异(P0.05),外周血CEA mRNA阳性率无显著差异。结论:大肠癌引流静脉血微转移是大肠癌肝转移的发生的早期阶段,引流静脉血CEA mRNA的表达能更早期反映出大肠癌患者微转移的发生,引流静脉微转移发生率与肿瘤分化程度、浸润深度、TNM分期、淋巴结转移、远处转移相关,是反映大肠癌生物学行为的指标之一,手术对大肠癌血循环微转移有促进作用。     

CEAmRNA在大肠癌患者微转移早期预测中的意义

目的：大肠癌是最常见的恶性肿瘤之一,血行转移是大肠癌根治性手术失败的原因之一,在根治性切除肿瘤患者中,有大部分患者死于肿瘤的复发和转移,因此早期发现大肠癌微转移,对于延长患者预后指导下一步治疗具有重要意义。本研究已检测大肠癌患者外周血和引流静脉血中CEAmRNA的表达,以探索手术操作和微转移的关系,以及引流静脉血中微转移的发生与临床病理因素的关系,探讨早期发现大肠癌血循环微转移的意义。方法：应用逆转录多聚酶链式反应（RT-PCR）法检测大肠癌患者手术前,手术后外周血及引流静脉血液中的CEAmRNA水平。结果：（1）大肠癌患者术前外周血CEAmRNA阳性率26．7％（16／60）,引流静脉血阳性率48.3％（29／60）,引流静脉血明显高于外周静脉血（P〈0．05）。（2）大肠癌引流静脉血中CEAmRNA在肿瘤大于5厘米者、DukesC期、中低分化程度、有淋巴转移者、浸及浆膜者比外周静脉血更有统计学上的意义。（3）手术前后引流静脉血CEAmRNA阳性率具有显著差异（P〈O．05）,外周血CEAmRNA阳性率无显著差异。结论：大肠癌引流静脉血微转移是大肠癌肝转移的发生的早期阶段,引流静脉血CEAmRNA的表达能更早期反映出大肠癌患者微转移的发生,引流静脉微转移发生率与肿瘤分化程度、浸润深度、TNM分期、淋巴结转移、远处转移相关,是反映大肠癌生物学行为的指标之一,手术对大肠癌血循环微转移有促进作用。     

Clinical Problems: Hypercalcaemia in Patients with Advanced Mammary Cancer

Hypercalcaemia and hypercalciuria are common complications of advanced mammary cancer. Of 127 patients with the disease 63 (49·5%) had some abnormality of calcium balance. Eighteen (14%) of these patients developed severe progressive hypercalcaemia and became acutely ill.Most patients had skeletal metastases, and the usual cause of hypercalcaemia was rapid destruction of bone by the cancer. One patient with severe uncontrollable hypercalcaemia and minimal skeletal involvement probably developed the complication due to inappropriate secretion of a parathyroid-hormone-like substance by massive hepatic deposits.Severe hypercalcaemia was controlled successfully in 13 of the 18 patients, the serum calcium levels returning to normal and the acute symptoms disappearing. Unfortunately, successful correction of the hypercalcaemia rarely was followed by prolonged survival from the underlying malignant disease. The incidence of subsequent objective response to pituitary ablation was less than usual, and only three patients survived for more than one year after the episode of hypercalcaemia.     

MiR-422a as a Potential Cellular MicroRNA Biomarker for Postmenopausal Osteoporosis

Background

MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that regulate gene expression by targeting mRNAs. Recently, miRNAs have been shown to play important roles in the etiology of various diseases. However, little is known about their roles in the development of osteoporosis. Circulating monocytes are osteoclast precursors that also produce various factors important for osteoclastogenesis. Previously, we have identified a potential biomarker miR-133a in circulating monocytes for postmenopausal osteoporosis. In this study, we aimed to further identify significant miRNA biomarkers in human circulating monocytes underlying postmenopausal osteoporosis.

Methodology/Principal Findings

We used ABI TaqMan miRNA array followed by qRT-PCR validation in human circulating monocytes from 10 high BMD and 10 low BMD postmenopausal Caucasian women to identify miRNA biomarkers. MiR-422a was up-regulated with marginal significance (P = 0.065) in the low compared with the high BMD group in the array analysis. However, a significant up-regulation of miR-422a was identified in the low BMD group by qRT-PCR analysis (P = 0.029). We also performed bioinformatic target gene analysis and found several potential target genes of miR-422a which are involved in osteoclastogenesis. Further qRT-PCR analyses of the target genes in the same study subjects showed that the expression of five of these genes (CBL, CD226, IGF1, PAG1, and TOB2) correlated negatively with miR-422a expression.

Conclusions/Significance

Our study suggests that miR-422a in human circulating monocytes (osteoclast precursors) is a potential miRNA biomarker underlying postmenopausal osteoporosis.